Although shock wave lithotripsy (SWL) is used routinely for the comminution of kidney and upper urinary stones, treatment efficiency has not been improved in the past twenty years. Further, renal injuries such as hemorrhage and kidney edema are often observed following lithotripsy, and the long-term clinical consequences of SWL (especially in pediatric and elderly patients) are still under investigation. Hence, it is imperative to improve the treatment efficiency of SWL while reducing its deleterious effects on renal tissues. The overall hypothesis of this project is that cavitation, the formation and subsequent violent expansion and collapse of small gas/vapor bubbles in a lithotripter field, is an important physical phenomenon relating to both stone comminution and tissue injury. However, the underlying mechanisms by which cavitation contributes to stone comminution and to tissue injury are different, making it possible to manipulate selectively bubble dynamics to enhance stone comminution while reducing tissue injury. In the current funding period, we have demonstrated that 1) controlled, forced collapse of cavitation bubbles can significantly improve stone comminution in vitro, and 2) SWL-induced rapid, large intraluminal bubble expansion can rupture capillary and small blood vessels if cavitation nuclei greater than 10 nm in diameter exist in vivo. Based on these observations, we propose four new specific aims to better understand the mechanisms of stone comminution and to develop novel cavitation control techniques to improve the efficiency and safety of SWL under clinically relevant conditions. A systematic approach will be undertaken to 1) assess the relative contribution of spalling vs. cavitation in stone comminution, 2) develop a piezoelectric annular array (PEAA) shock wave generator that can be retrofitted on a Domier HM-3 lithotripter to achieve in situ cavitation control, 3) explore novel techniques to suppress large intraluminal bubble expansion in SWL in order to reduce vascular injury, and 4) optimize the design of clinical lithotripters to maximize stone comminution while minimizing tissue injury. Since these techniques under development can be upgraded on existing clinical lithotripters, once successful, they could produce immediate clinical and economic benefits to the overall management of urolithiasis.